With a trial win in certain acute myeloid leukemia (AML) patients, Servier’s cancer med Tibsovo is primed to break into front-line use as a combo treatment for patients who can't handle intensive chemotherapy. Meanwhile, the drug may now have the data it needs to clinch an approval in Europe, a Servier executive said in a recent interview.
Servier announced the trial win in August and is now presenting details today at the American Society of Hematology’s (ASH's) 63rd annual meeting. Even prior to noting the trial's success, the Tibsovo combo’s benefit was so apparent in that study, dubbed AGILE, that an independent data monitoring committee recommended halting further enrollment early, which Servier did.
The IDH inhibitor is already approved as a solo agent in previously treated IDH1-mutated AML and for certain newly diagnosed patients who aren’t eligible for intensive chemotherapy. The phase 3 AGILE win takes Tibsovo's monotherapy foundation and moves things “one step further” with a “compelling combination approach” in newly diagnosed, intensive chemotherapy ineligible patients, Susan Pandya, M.D., head of cancer metabolism global development oncology and immuno-oncology at Servier, told Fierce Pharma.
The drug in August also won a green light in previously treated cholangiocarcinoma—a rare bile duct cancer—with an IDH1 mutation. The approval made Tibsovo the first targeted therapy for those patients, Servier said at the time.
As for what makes the AGILE readout in AML so "exciting," it builds on Servier’s previous understandings about its IDH portfolio and also shows “additivity with the standard chemotherapy backbone of azacytidine,” Pandya said. Azacitidine is the generic name for Bristol Myers Squibb’s Vidaza. What’s more, this additivity “not only has impressive response rates and event-free survival outcomes but probably most importantly, overall survival improvement in patients receiving the combination versus azacytidine alone,” she added.
While the drug is only approved as a single agent, about half of its use in 2020 was in combination therapies, Darrin Miles, chief commercial officer of Tibsovo's previous owner, Agios, said earlier this year. Agios reported $121 million in Tibsovo sales last year, with Miles predicting the med could reap somewhere in the range of $160 million to $170 million in 2021.
In the 146-subject AGILE study of previously untreated patients with IDH1-mutated AML who weren’t eligible for induction chemotherapy, Tibsovo plus BMS' Vidaza “significantly” trumped Vidaza alone at extending the time to treatment failure, tumor relapse or death, the company said. Event-free survival was statistically significant in favor of Tibsovo plus Vidaza, Servier said in its ASH presentation.
Additionally, the median overall survival time for patients on the combo was 24 months versus 7.9 months in the Vidaza arm. Complete remission was observed in 47.2% of patients in the Tibsovo cohort, compared to 14.9% in the control. The median time for Tibsovo patients to hit complete remission was 4.3 months, versus 3.8 months in the Vidaza group.
The drug also won out on other secondary endpoints like complete remission with partial hematologic recovery and objective response.
With promising data in hand, the company is now actively engaged with regulators, Pandya said.
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Tibsovo’s previous owner, Agios, had to withdraw an EU application in relapsed or refractory AML after reviewers at the European Medicines Agency said they wouldn’t approve the drug on tumor shrinkage data alone. Both of the drug’s FDA nods are based on small single-arm trials that showed the IDH inhibitor could clear cancer.
"I think some of the challenge previously is that you had a single arm phase 1 study, where we were seeking approval ex-U.S.," Pandya said.
With AGILE, Servier now has data from a “different caliber of a clinical trial, and I think that would meet the regulatory standards around the globe,” she added.
Safety was generally on par with that of Tibsovo in other studies, she added. No new toxicities manifested, which is “reassuring,” and the trial had relatively low discontinuation rates because of side effects, which speaks to the tolerability of the Tibsovo-Vidaza combination, Pandya said.
The most common reported side effects were nausea, vomiting, diarrhea, pyrexia, anemia, febrile neutropenia, thrombocytopenia, constipation and pneumonia, Servier said.
Should an approval come through, doctors should be happy to have another AML weapon at their disposal, Pandya added. The chemo-ineligible patients Servier studied are unlikely to ultimately receive a transplant, which is the only known curative therapy for the disease, Pandya said.
"So, keeping that in mind, I think it is important to have options for patients who aren't eligible for intensive chemotherapy," she added. "And those options can span from targeted combination approaches, as is the case in the setting with IDH1-mutant AML, or the setting of more a more general treatment approach."
Doctors "like the option to have options," and that's especially true in any setting where a cure is unlikely, Pandya said.
Editor's note: This story was updated to include the correct overall survival stat. Median overall survival time for patients on the Tibsovo combo was 24 months.